Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZBZ224)

• DOT Name: FMR1-interacting protein NUFIP2 (NUFIP2)
• Synonyms: 82 kDa FMRP-interacting protein; 82-FIP; Cell proliferation-inducing gene 1 protein; FMRP-interacting protein 2; Nuclear FMR1-interacting protein 2
• Gene Name: NUFIP2
• Related Disease:
  Autism
  Allergic asthma
  Alzheimer disease
  Asthma
  Astrocytoma
  Attention deficit hyperactivity disorder
  Bipolar disorder
  Cerebellar ataxia
  Cognitive impairment
  Fragile X-associated tremor/ataxia syndrome
  Parkinson disease
  Pervasive developmental disorder
  Schizophrenia
  Trichohepatoenteric syndrome
  Zika virus infection
  Atrial septal defect
  Congenital glaucoma
  Juvenile open angle glaucoma
  Neurodevelopmental disorder
  Epilepsy
  Autism spectrum disorder
  Intellectual disability
  Mental disorder
  Neoplasm
• UniProt ID: NUFP2_HUMAN
• Pfam ID: PF15293
• Sequence:
  MEEKPGQPQPQHHHSHHHPHHHPQQQQQQPHHHHHYYFYNHSHNHHHHHHHQQPHQYLQH
  GAEGSPKAQPKPLKHEQKHTLQQHQETPKKKTGYGELNGNAGEREISLKNLSSDEATNPI
  SRVLNGNQQVVDTSLKQTVKANTFGKAGIKTKNFIQKNSMDKKNGKSYENKSGENQSVDK
  SDTIPIPNGVVTNNSGYITNGYMGKGADNDGSGSESGYTTPKKRKARRNSAKGCENLNIV
  QDKIMQQETSVPTLKQGLETFKPDYSEQKGNRVDGSKPIWKYETGPGGTSRGKPAVGDML
  RKSSDSKPGVSSKKFDDRPKGKHASAVASKEDSWTLFKPPPVFPVDNSSAKIVPKISYAS
  KVKENLNKTIQNSSVSPTSSSSSSSSTGETQTQSSSRLSQVPMSALKSVTSANFSNGPVL
  AGTDGNVYPPGGQPLLTTAANTLTPISSGTDSVLQDMSLTSAAVEQIKTSLFIYPSNMQT
  MLLSTAQVDLPSQTDQQNLGDIFQNQWGLSFINEPSAGPETVTGKSSEHKVMEVTFQGEY
  PATLVSQGAEIIPSGTEHPVFPKAYELEKRTSPQVLGSILKSGTTSESGALSLEPSHIGD
  LQKADTSSQGALVFLSKDYEIESQNPLASPTNTLLGSAKEQRYQRGLERNDSWGSFDLRA
  AIVYHTKEMESIWNLQKQDPKRIITYNEAMDSPDQ
• Function: Binds RNA.

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism	DISV4V1Z	Definitive	Biomarker	[1]
Allergic asthma	DISHF0H3	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Asthma	DISW9QNS	Strong	Genetic Variation	[2]
Astrocytoma	DISL3V18	Strong	Biomarker	[4]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Biomarker	[5]
Bipolar disorder	DISAM7J2	Strong	Genetic Variation	[6]
Cerebellar ataxia	DIS9IRAV	Strong	Biomarker	[7]
Cognitive impairment	DISH2ERD	Strong	Biomarker	[8]
Fragile X-associated tremor/ataxia syndrome	DISKB25R	Strong	Genetic Variation	[9]
Parkinson disease	DISQVHKL	Strong	Biomarker	[10]
Pervasive developmental disorder	DIS51975	Strong	Genetic Variation	[11]
Schizophrenia	DISSRV2N	Strong	Biomarker	[12]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Altered Expression	[13]
Zika virus infection	DISQUCTY	Strong	Biomarker	[14]
Atrial septal defect	DISJT76B	moderate	Biomarker	[15]
Congenital glaucoma	DISHN3GO	moderate	Biomarker	[15]
Juvenile open angle glaucoma	DISZ43T5	moderate	Biomarker	[15]
Neurodevelopmental disorder	DIS372XH	moderate	Genetic Variation	[16]
Epilepsy	DISBB28L	Disputed	Biomarker	[5]
Autism spectrum disorder	DISXK8NV	Limited	Biomarker	[17]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[18]
Mental disorder	DIS3J5R8	Limited	Biomarker	[19]
Neoplasm	DISZKGEW	Limited	Biomarker	[20]

9 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of FMR1-interacting protein NUFIP2 (NUFIP2).	[21]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of FMR1-interacting protein NUFIP2 (NUFIP2).	[22]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of FMR1-interacting protein NUFIP2 (NUFIP2).	[23]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of FMR1-interacting protein NUFIP2 (NUFIP2).	[24]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of FMR1-interacting protein NUFIP2 (NUFIP2).	[25]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of FMR1-interacting protein NUFIP2 (NUFIP2).	[27]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of FMR1-interacting protein NUFIP2 (NUFIP2).	[28]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of FMR1-interacting protein NUFIP2 (NUFIP2).	[30]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of FMR1-interacting protein NUFIP2 (NUFIP2).	[31]

4 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of FMR1-interacting protein NUFIP2 (NUFIP2).	[26]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of FMR1-interacting protein NUFIP2 (NUFIP2).	[29]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of FMR1-interacting protein NUFIP2 (NUFIP2).	[26]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of FMR1-interacting protein NUFIP2 (NUFIP2).	[26]

References

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• [2] Positional identification of an asthma susceptibility gene on human chromosome 5q33.Am J Respir Crit Care Med. 2005 Jul 15;172(2):183-8. doi: 10.1164/rccm.200409-1223OC. Epub 2005 May 5.
• [3] Opposite Dysregulation of Fragile-X Mental Retardation Protein and Heteronuclear Ribonucleoprotein C Protein Associates with Enhanced APP Translation in Alzheimer Disease.Mol Neurobiol. 2016 Jul;53(5):3227-3234. doi: 10.1007/s12035-015-9229-8. Epub 2015 Jun 6.
• [4] Fragile X mental retardation protein promotes astrocytoma proliferation via the MEK/ERK signaling pathway.Oncotarget. 2016 Nov 15;7(46):75394-75406. doi: 10.18632/oncotarget.12215.
• [5] Downregulation of tonic GABAergic inhibition in a mouse model of fragile X syndrome.Cereb Cortex. 2009 Jul;19(7):1515-20. doi: 10.1093/cercor/bhn159. Epub 2008 Sep 11.
• [6] Metabotropic glutamate receptors as emerging research targets in bipolar disorder.Psychiatry Res. 2017 Nov;257:327-337. doi: 10.1016/j.psychres.2017.07.059. Epub 2017 Jul 31.
• [7] Acute Ethanol Produces Ataxia and Induces Fmr1 Expression via Histone Modifications in the Rat Cerebellum.Alcohol Clin Exp Res. 2019 Jun;43(6):1191-1198. doi: 10.1111/acer.14044. Epub 2019 May 14.
• [8] Metformin for Treatment of Fragile X Syndrome and Other Neurological Disorders.Annu Rev Med. 2019 Jan 27;70:167-181. doi: 10.1146/annurev-med-081117-041238. Epub 2018 Oct 26.
• [9] Quantitative Evaluation of Toxic Polyglycine Biosynthesis and Aggregation in Cell Models Expressing Expanded CGG Repeats.Front Genet. 2018 Jun 19;9:216. doi: 10.3389/fgene.2018.00216. eCollection 2018.
• [10] Loss of fragile X mental retardation protein precedes Lewy pathology in Parkinson's disease.Acta Neuropathol. 2020 Feb;139(2):319-345. doi: 10.1007/s00401-019-02099-5. Epub 2019 Nov 25.
• [11] Pharmacological Rescue of Hippocampal Fear Learning Deficits in Fragile X Syndrome.Mol Neurobiol. 2018 Jul;55(7):5951-5961. doi: 10.1007/s12035-017-0819-5. Epub 2017 Nov 11.
• [12] Rare Risk Variants Identification by Identity-by-Descent Mapping and Whole-Exome Sequencing Implicates Neuronal Development Pathways in Schizophrenia and Bipolar Disorder.Mol Neurobiol. 2018 Sep;55(9):7366-7376. doi: 10.1007/s12035-018-0922-2. Epub 2018 Feb 6.
• [13] Fragile X syndrome: a preclinical review on metabotropic glutamate receptor 5 (mGluR5) antagonists and drug development.Psychopharmacology (Berl). 2014 Mar;231(6):1217-26. doi: 10.1007/s00213-013-3330-3.
• [14] Fragile X mental retardation protein is a Zika virus restriction factor that is antagonized by subgenomic flaviviral RNA.Elife. 2018 Dec 4;7:e39023. doi: 10.7554/eLife.39023.
• [15] Familial transmission risk of infantile glaucoma in Australia.Ophthalmic Genet. 2006 Sep;27(3):93-7. doi: 10.1080/13816810600870843.
• [16] The emerging fragile X premutation phenotype: evidence from the domain of social cognition.Brain Cogn. 2005 Feb;57(1):53-60. doi: 10.1016/j.bandc.2004.08.020.
• [17] Fragile X Mental Retardation Protein positively regulates PKA anchor Rugose and PKA activity to control actin assembly in learning/memory circuitry.Neurobiol Dis. 2019 Jul;127:53-64. doi: 10.1016/j.nbd.2019.02.004. Epub 2019 Feb 13.
• [18] hnRNP Q Regulates Internal Ribosome Entry Site-Mediated fmr1 Translation in Neurons.Mol Cell Biol. 2019 Feb 4;39(4):e00371-18. doi: 10.1128/MCB.00371-18. Print 2019 Feb 15.
• [19] Gene-set analysis shows association between FMRP targets and autism spectrum disorder.Eur J Hum Genet. 2017 Jun;25(7):863-868. doi: 10.1038/ejhg.2017.55. Epub 2017 Apr 19.
• [20] The fragile X mental retardation protein regulates tumor invasiveness-related pathways in melanoma cells.Cell Death Dis. 2017 Nov 16;8(11):e3169. doi: 10.1038/cddis.2017.521.
• [21] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [22] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [23] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [24] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [25] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [26] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [27] Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells. Neoplasia. 2006 Sep;8(9):758-71.
• [28] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [29] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [30] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [31] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.